Photocontrolled Exposure of Pro‐apoptotic Peptide Sequences in LOV Proteins Modulates Bcl‐2 Family Interactions

LOV domains act as biomolecular sensors for light, oxygen or the environment's redox potential. Conformational changes upon the formation of a covalent cysteinyl flavin adduct are propagated through hydrogen‐bonding networks in the core of designed hybrid phototropin LOV2 domains that incorporate the Bcl homology region 3 (BH3) of the key pro‐apoptotic protein BH3‐interacting‐domain death agonist (BID). The resulting change in conformation of a flanking amphiphilic α‐helix creates a light‐dependent optogenetic tool for the modulation of interactions with the anti‐apoptotic B‐cell leukaemia‐2 (Bcl‐2) family member Bcl‐x(L).